The goal of this project is to define T cell immune responses to the Human Immunodeficiency Virus (HIV). Mechanisms both of protective as well as deleterious cellular immune reactions to many different epitopes of the HIV envelope and core proteins will be examined. The project uses recombinant viral proteins, glycoproteins and synthetic peptides to better define the antigenic epitopes responsible for T cell reactions to intact HIV. Lymphocytes will be identified which mediate cytotoxic, proliferative and other antiviral responses in HIV infected individuals and control. Cloned T cell lines will be developed which are specific for protective responses to HIV. Such clones will be used as tools to study restriction of T cell immunity by the human major histocompatibility complex. Since maladaptive host responses such as autoimmunity contribute to helper cell deficiency in AIDS, autotoxic cellular immune reactions to HIV will be explored. The large library of clones already available will facilitate a genetic and functional analysis of cellular autoimmunity. Some HIV antigens may be immunosuppressive by blocking CD4 T cell receptors or other lymphocyte surface molecules. Our work is directed at identifying those portions of the HIV genome which encode for the suppressive epitopes. The array of cellular immune assays we develop will be applied to clinical epidemiologic studies in conjunction with the San Francisco Men's Health Project to better understand the balance between protective and harmful immunity to HIV throughout the entire spectrum of HIv infections. The increased knowledge that these studies provide about protective as well as maladaptive host responses to HIV that should lead to rational development of safe and efficacious vaccines and novel immunotherapeutic strategies.